In vivo fluorescence imaging of exogenous enzyme activity in the gastrointestinal tract.

Exogenous enzymes are administered orally to treat several diseases, such as pancreatic insufficiency and lactose intolerance. Due to the proteinaceous nature of enzymes, they are subject to inactivation and/or digestion in the gastrointestinal (GI) tract. Here we describe a convenient fluorescence-based assay to monitor the activity of therapeutic enzymes in real time in vivo in the GI tract.

New pharmaceutical applications for macromolecular binders.

Macromolecular binders consist of polymers, dendrimers, and oligomers with binding properties for endogenous or exogenous substrates. This field, at the frontier of host/guest chemistry and pharmacology, has met a renewed interest in the past decade due to the clinical success of several sequestrants, like sevelamer hydrochloride (Renagel®) or sugammadex (Bridion®). In many instances, multivalent binding by the macromolecular drugs can modify the properties of the substrate, and may prevent it from reaching its site of action and/or trigger a biological response.

Development and physico-chemical characterization of a liposomal formulation of istaroxime.

Istaroxime, an investigational new drug that targets defective Ca(2+) cycling without compromising cardiac efficiency, may represent a promising and safe treatment of both acute and chronic heart failure. Even though the compound demonstrated good tolerability in a phase I/II safety study, symptoms related to the gastro-intestinal tract and pain at the injection site were reported as the most frequent side effects. The aim of this study was to encapsulate istaroxime in a drug delivery system (DDS) that could minimize the pain perceived upon administration.

Language lateralization in individuals with callosal agenesis: an fMRI study.

Since the seminal work of Broca in 1861, it is well established that language is essentially processed in the left hemisphere. However, the origin of hemispheric specialization remains controversial. Some authors posit that language lateralization is genetically determined, while others have suggested that hemispheric specialization develops with age.

AUXIN RESPONSE FACTOR8 regulates Arabidopsis petal growth by interacting with the bHLH transcription factor BIGPETALp.

Plant organ growth and final size are determined by coordinated cell proliferation and expansion. The BIGPETALp (BPEp) basic helix-loop-helix (bHLH) transcription factor was shown to limit Arabidopsis thaliana petal growth by influencing cell expansion. We demonstrate here that BPEp interacts with AUXIN RESPONSE FACTOR8 (ARF8) to affect petal growth.

Co-encapsulation of magnetic nanoparticles and doxorubicin into biodegradable microcarriers for deep tissue targeting by vascular MRI navigation.

Magnetic tumor targeting with external magnets is a promising method to increase the delivery of cytotoxic agents to tumor cells while reducing side effects. However, this approach suffers from intrinsic limitations, such as the inability to target areas within deep tissues, due mainly to a strong decrease of the magnetic field magnitude away from the magnets. Magnetic resonance navigation (MRN) involving the endovascular steering of therapeutic magnetic microcarriers (TMMC) represents a clinically viable alternative to reach deep tissues.

Percutaneous aspiration irrigation drainage technique in the management of septic arthritis in children.

Background: Septic arthritis in childhood is a therapeutic emergency. The authors present their experience using an intermediate technique with the advantages of the percutaneous aspiration irrigation drainage: joint aspiration, irrigation, and declivious drainage.

Methods: All children were treated by joint aspiration under fluoroscopic control, large volume irrigation, and declivious nonsuction drainage associated with immobilization and intravenous antibiotics during 8 days to 10 days.

siRNA nanocarriers based on methacrylic acid copolymers.

Poly(ethylene glycol)-b-poly(propyl methacrylate-co-methacrylic acid) (PEG-b-P(PrMA-co-MAA) can be complexed with poly(amido amine) (PAMAM) dendrimers and nucleic acids to form pH-responsive nanosized core-shell type polyion complex micelles (PICMs). These PICMs have the ability to lose their shell and release the PAMAM/nucleic acid core under mildly acidic conditions such as those encountered in the endosomal compartment. In this work, pH-sensitive PICMs composed of PEG-b-P(PrMA-co-MAA), different PAMAMs, and siRNAs were prepared and characterized.

Gene delivery with bisphosphonate-stabilized calcium phosphate nanoparticles.

Nucleic acid drugs are promising new therapeutics, due to their possible applications in a wide variety of diseases and their strong targeting potential and associated lower off-target effects compared to conventional pharmaceuticals. However, their poor intracellular bioavailability and rapid degradation hinder their development as drugs. Therefore, efficient delivery is a major challenge.

Transmembrane pH-gradient liposomes to treat cardiovascular drug intoxication.

Injectable scavenging nanocarriers have been proposed as detoxifying agents when there are no specific antidotes to treat pharmacological overdoses. They act by capturing the drug in situ, thereby restricting distribution in tissues. In the clinic, the only systems used for that purpose are parenteral lipid emulsions, which are relatively inefficient in terms of uptake capacity.

Nanonization of megestrol acetate by laser fragmentation in aqueous milieu.

Nanonization is a simple and effective method to improve dissolution rate and oral bioavailability of drugs with poor water solubility. There is growing interest to downscale the nanocrystal production to enable early preclinical evaluation of new drug candidates when compound availability is scarce. The purpose of the present study was to investigate laser fragmentation to form nanosuspensions in aqueous solution of the insoluble model drug megestrol acetate (MA) using very little quantities of the drug.

Prevention measures and exploratory pharmacological treatments of celiac disease.

Increasing prevalence, protean clinical manifestations, and lack of pharmacological therapy make celiac disease (CD) a complex and highly relevant illness in gastroenterology. This chronic inflammatory disorder of the small intestine is caused by the ingestion of gluten containing cereals in genetically susceptible individuals, leading to a variety of gastrointestinal (GI) and non-GI manifestations. Awareness among physicians is growing due to accessible and highly accurate diagnostic and screening methods.

Quantitative imaging of lymphatic function with liposomal indocyanine green.

Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection.

Fabrication of paclitaxel nanocrystals by femtosecond laser ablation and fragmentation.

Nanonization, which involves formulating the drug powder as nanometer-sized particles, is a known method to improve drug absorption and allow the intravenous administration of insoluble drugs. This study investigated a novel femtosecond (fs) laser technique for the fabrication of nanocrystals in aqueous solution of the insoluble model drug paclitaxel. Two distinct methods of this technology, ablation and fragmentation, were investigated and the influence of laser power, focusing position and treatment time on the particle size, drug concentration, and degradation was studied.

Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

Background: High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.

Polymeric micelles for oral drug delivery.

In the case of chronic therapies, the oral route is often the preferred route for drug administration given its acceptability and convenience. However, various factors which limit drug absorption through the gastro-intestinal (GI) mucosa contribute to restricting the bioavailability of the drug, that is, the actual amount which reaches the bloodstream. Among these factors, poor drug permeability through the GI mucosa and/or low aqueous solubility are of central importance.

pH-Responsive molecular tweezers.

Molecular tweezers are dynamic devices that are able to switch from one conformation to another upon stimulation by an external trigger. In this work, we report a new water-soluble macromolecular carrier bearing a pH-responsive molecular tweezer, whose affinity for a substrate depends on the external pH. The conformational change of the switching unit was evidenced by (1)H NMR spectroscopy, and fluorescence studies conducted in aqueous media demonstrated the ability of the carrier to bind to substrates in a pH-dependent fashion.

Lumbopelvic stabilization with external fixator in a patient with lumbosacral agenesis.

A case of caudal regression syndrome in which rehabilitation was obtained by lumbopelvic distraction and stabilization with external fixation Orthofix(®) is presented. The objective of the study is to describe the benefit of spine external fixator in caudal regression syndrome. Caudal regression syndrome is a rare and sporadic neural defect of distal spinal segments affecting the development of the spinal cord.

In vivo evaluation of pH-sensitive polymer-based immunoliposomes targeting the CD33 antigen.

The purpose of this study was to evaluate in vivo a targeted pH-sensitive liposomal formulation tailored to promote the efficient intracellular delivery of 1-beta-d-arabinofuranosylcytosine (ara-C) to human myeloid leukemia cells. Specifically, pH-sensitive immunoliposomes were obtained by anchoring a copolymer of dioctadecyl, N-isopropylacrylamide and methacrylic acid in bilayers of PEGylated liposomes (LP) and by coupling the whole anti-CD33 monoclonal antibody (mAb) or its Fab' fragments. Their pharmacokinetic and biodistribution profiles were assessed in Balb/c and leukemic HL60-bearing immunodepressed (SCID) mice.

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer's disease.

Organogels can be prepared by immobilizing an organic phase into a three-dimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer's disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days.

Aminated linear and star-shape poly(glycerol methacrylate)s: synthesis and self-assembling properties.

Over the past 10 years, polyglycerols and their structurally related analogs have received considerable attention in the biomedical field. Poly(glycidyl methacrylate) (PGMA) is a versatile polymer because its pendant epoxide groups can be opened with different functional groups to generate poly(glycerol methacrylate)s (PGOHMA) derivatives. In this work, linear and star-shape PGMAs were synthesized by atom transfer radical polymerization and then functionalized with four different amines by ring-opening addition.

Serum-stable, long-circulating, pH-sensitive PEGylated liposomes.

pH-sensitive liposomes have been designed to deliver active compounds, specifically to acidic intracellular organelles and to augment their cytoplasmic concentrations. These systems combine the protective effects of other liposomal formulations with specific environment-controlled drug release. They are stable at physiological pH, but abruptly discharge their contents when endocytosed into acidic compartments, allowing the drug to be released before it is exposed to the harsh environment of lysosomes.